Chronic lymphocytic leukemia (CLL) is characterized by the relentless accumulation of monoclonal B cells with the appearance of small mature lymphocytes and a characteristic CD5 and CD19 co-expression immunophenotype. The incidence of CLL is lower in Asian countries than in Western countries, where CLL is the most common leukemia. To investigate CLLU1 expression in CLL and explore the relationship between CLLU1 expression and alternative prognostic markers, we measured CLLU1 expression levels by semiquantitative RT-PCR in a cohort of 50 Chinese patients with CLL. Analyses of IgVH somatic mutational status, ZAP-70 expression, CD38 expression, and chromosomal aberrations were also performed. The expression of CLLU1 mRNA was determined in 26 of the 50 cases (52%), among which 7 at Binet A (7/21, 33.33%) and 19 at Binet B + C (19/29, 65.52%). The expression levels of CLLU1 were significantly increased in B + C CLL patients at Binet stage compared with those at Binet stage A (P = 0.005). Data for the IgVH somatic mutational status were available for 20 patients with known CLLU1 expression. Five (25%) patients, all expressed CLLU1 mRNA, displayed unmutated IgVH gene usage. While in 15 patients (15/20, 75%) with mutated IgVH gene, only 6 were CLLU1 positive. Patients with unmutated IgVH genes expressed higher levels of CLLU1 than did those with IgVH mutations (P < 0.05). Among 24 CD38(+)-CLL cases, 17 (70.83%) were CLLU1 positive, whereas only 9 (34.62%) positive cases were identified in 26 CD38(-)-CLL patients. Thus, the expression of CLLU1 in CD38(+)-CLL was significantly higher than that in CD38(-)-CLL. However, no significant difference of CLLU1 expression was found between ZAP-70(+) (14/22, 63.64%) and ZAP-70(-) (12/28, 42.86%) patients (P > 0.05). We conclude that CLLU1 expression was significantly associated with clinical stages, IgVH somatic mutational status and CD38 expression, and might be an important prognostic factor in CLL patients.